Darolutamide and Survival in Metastatic, Hormone-Sensitive Prostate Cancer.

BACKGROUND: Darolutamide is a potent androgen-receptor inhibitor that has been associated with increased overall survival among patients with nonmetastatic, castration-resistant prostate cancer. Whether a combination of darolutamide, androgen-deprivation therapy, and docetaxel would increase survival among patients with metastatic, hormone-sensitive prostate cancer is unknown. METHODS: In this international, phase 3 trial, we randomly assigned patients with metastatic, hormone-sensitive prostate cancer in a 1:1 ratio to receive darolutamide (at a dose of 600 mg [two 300-mg tablets] twice daily) or matching placebo, both in combination with androgen-deprivation therapy and docetaxel. The primary end point was overall survival. RESULTS: The primary analysis involved 1306 patients (651 in the darolutamide group and 655 in the placebo group); 86.1% of the patients had disease that was metastatic at the time of the initial diagnosis. At the data cutoff date for the primary analysis (October 25, 2021), the risk of death was significantly lower, by 32.5%, in the darolutamide group than in the placebo group (hazard ratio 0.68; 95% confidence interval, 0.57 to 0.80; P<0.001). Darolutamide was also associated with consistent benefits with respect to the secondary end points and prespecified subgroups. Adverse events were similar in the two groups, and the incidences of the most common adverse events (occurring in ≥10% of the patients) were highest during the overlapping docetaxel treatment period in both groups. The frequency of grade 3 or 4 adverse events was 66.1% in the darolutamide group and 63.5% in the placebo group; neutropenia was the most common grade 3 or 4 adverse event (in 33.7% and 34.2%, respectively). CONCLUSIONS: In this trial involving patients with metastatic, hormone-sensitive prostate cancer, overall survival was significantly longer with the combination of darolutamide, androgen-deprivation therapy, and docetaxel than with placebo plus androgen-deprivation therapy and docetaxel, and the addition of darolutamide led to improvement in key secondary end points. The frequency of adverse events was similar in the two groups. (Funded by Bayer and Orion Pharma; ARASENS ClinicalTrials.gov number, NCT02799602.).

Replacement of Milk and Dairy Products with Soy-Based Alternatives-How to Avoid Nutrient Deficiencies in a Milk-Free Diet?

BACKGROUND: In Germany, milk and dairy products are increasingly replaced by their plant-based alternatives. Although they can be used as substitutes, they differ significantly in their nutrient composition; thus, substitution could lead to nutrient deficiencies. So far, there are no food-based dietary recommendations that show which foods can replace milk and dairy products in a healthy way when switching to a plant-based substitute. OBJECTIVES: Against this background, the question arises as to how to ensure adequate intake of critical nutrients when plant-based alternatives are consumed instead of milk and dairy products. To answer this question, this study aims to analyze what dietary changes would be required to avoid possible nutrient deficiencies and what types of foods can be consumed instead. METHODS: To answer the research question, 3 different models are compared using the linear programming method: healthy diets with 1) milk and dairy products, 2) nonfortified plant-based alternatives, and 3) fortified plant-based alternatives. The models are applied to omnivorous, pescatarian, and vegetarian diet types. RESULTS: The results show that when consuming nonfortified soy alternatives, an adequate supply of calcium and, in the case of a vegetarian diet, vitamin B12 can only be achieved if significant dietary changes are made compared to the average diet. This includes a significantly higher consumption of fruit and vegetables, whereby within the groups, calcium-rich varieties should be chosen (e.g., green leafy vegetables). When consuming fortified soy-based alternatives instead, the absence of milk and dairy products can be well compensated by the nutrients currently added to commercially available products. CONCLUSIONS: Given the trend to consume less milk and dairy products or to abstain from them altogether, public health measures should point out possible nutrient deficiencies as well as necessary dietary changes, especially because in Germany, many plant-based alternatives are not fortified.

Additional costs of lactose-reduced diets: lactose-free dairy product substitutes are a cost-effective alternative for people with lactose intolerance.

OBJECTIVE: People with lactose intolerance have to limit their consumption of lactose-containing dairy products which are a main source of Ca. In particular, for low-income people it is of interest which alternative diet form rich in Ca leads to the lowest additional costs. This study aims to calculate the additional costs of lactose-reduced diets and to show which of different options represent the most cost-effective alternative within a lactose-reduced diet. DESIGN: Using linear programming, food baskets with different lactose contents were calculated and were compared to a basic model, reflecting a normal diet without a limitation of lactose. By comparing the costs and the composition of the food baskets, recommendations for a lactose-reduced diet were derived. SETTING: Germany. PARTICIPANTS: A consumer panel dataset representative for Germany is used for the calculations. Information on prices and nutrients is derived from the 9429 adult households without children, and information on consumed food quantities from the 3046 single households. RESULTS: The minimum additional food costs depend on the severity of lactose intolerance and range from 0·2 % to 6·1 % per month. It was found that the greatest adjustments due to lactose reduction could be observed within the dairy product group. In this group, with a rising lactose limit, normal milk was increasingly replaced by lactose-free milk. CONCLUSION: It was shown that a lactose-reduced diet is generally associated with higher food costs. When suffering from lactose intolerance, switching to lactose-free milk seems to be the most cost-effective way to cover nutrient requirements.

What are the potential preventive population-health effects of a tax on processed meat? A quantitative health impact assessment for Germany.

The International Agency for Research on Cancer considers processed meat to be carcinogenic. Further, processed meat is associated with diabetes, ischemic heart disease (IHD) and all-cause mortality. We aimed to assess health gains of four processed meat taxation scenarios in comparison to the reference and a minimum-risk-exposure-scenario. To estimate the shift in processed meat intake following respective taxes, we calculated price elasticities for processed meat. DYNAMO-HIA was used to dynamically project policy-attributable differences in the prevalence of diseases and deaths. In projection year 10, an extra 9300 males and 4500 females would be alive under the lowest tax scenario (4% tax), compared to the reference scenario. Prevalent IHD, diabetes and colorectal cancer cases in males would be 8400, 9500 and 500 lower, respectively, and there would be 4600, 7800 and 300 less cases in females. Of the respective death and disease reduction that would be achieved under the minimum-risk-exposure-scenario, the lowest tax reaches 2.84% (colorectal cancer in males) to 6.02% (diabetes in females). Under the highest tax scenario (33.3% tax), an extra 76,700 males and 37,100 females would be alive, compared to the reference scenario. Prevalent IHD, diabetes and colorectal cancer cases would be 70,800, 77,900 and 4900 lower in males and 29,900, 48,900 and 2300 lower in females, which represents 27.84% (colorectal cancer in males) to 37.76% (diabetes in females) of the maximal preventable death and disease burden. Further research needs to examine to what extent these health benefits are outweighed by a simultaneous tax-induced decrease in fish intake.

Convenience-based food purchase patterns: identification and associations with dietary quality, sociodemographic factors and attitudes.

OBJECTIVE: The present study aimed to derive food purchase patterns considering the convenience level of foods. Associations between identified patterns and dietary quality were analysed, as well as household characteristics associated with the dietary patterns. DESIGN: A Convenience Food Classification Scheme (CFCS) was developed. After classifying basic food groups into the CFCS, the formed groups were used to apply a factor analysis to identify convenience-based food purchase patterns. For these patterns nutrient and energy densities were examined. Using regression analysis, associations between the adherence to the patterns and household characteristic and attitude variables were analysed. SUBJECTS: The study used representative German food purchase data from 2011. Approximately 12 million purchases of 13 131 households were recorded in these data. RESULTS: Three convenience-based patterns were identified: a low-convenience, a semi-convenience and a ready-to-eat food pattern. Tighter adherence to the semi-convenience pattern was shown to result in the lowest nutrient and highest energy densities. Important factors influencing adherence to the patterns were household size, presence of children and attitudes. Working full-time was negatively associated with adherence to the low-convenience pattern and positively with the ready-to-eat pattern. CONCLUSIONS: Convenience foods were an important part of households' food baskets which in some cases led to lower nutritional quality. Therefore, it is important to offer convenience foods higher in nutrient density and lower in energy density. Interventions targeted on enhancing cooking skills could be an effective strategy to increase purchases of unprocessed foods, which, in turn, could also contribute to an improved diet quality.

Food purchase patterns: empirical identification and analysis of their association with diet quality, socio-economic factors, and attitudes.

BACKGROUND: Empirically derived food purchase patterns provide information about which combinations of foods were purchased from households. The objective of this study was to identify what kinds of patterns exist, which level of diet quality they represent and which factors are associated with the patterns. METHODS: The study made use of representative German consumption data in which approximately 12 million food purchases from 13,125 households are recorded. In accordance with healthy diet criteria the food purchases were assigned to 18 food groups of the German Food Pyramid. Based on these groups a factor analysis with a principal component technique was applied to identify food patterns. For these patterns nutrient and energy densities were examined. Using regression analysis, associations between pattern scores and socio-economic as well as attitude variables, reflecting personal statements about healthy eating, were analyzed. RESULTS: In total, three food purchase patterns could be identified: a natural, a processed and a traditional one. The first one was characterized by a higher purchasing of natural foods, the second by an increased purchasing of processed foods and the third by a meat-oriented diet. In each pattern there were specific diet quality criteria that could be improved whereas others were in line with actual dietary guidelines. In addition to socio-demographic factors, attitudes were significantly associated with the purchase patterns. CONCLUSIONS: The findings of this study are interesting from a public health perspective, as it can be assumed that measures focusing on specific aspects of diet quality are more promising than general ones. However, it is a major challenge to identify the population groups with their specific needs of improvement. As the patterns were associated with both socio-economic and attitude variables these grouping criteria could be used to define target groups.

Association between the Healthy Eating Index-2010 and nutrient and energy densities of German households' food purchases.

Background: The USDA Healthy Eating Index (HEI) is used widely to measure diet quality because it allows a number of different applications. Although several evaluations of the HEI-2010 have already been carried out, there is lack of those which focus on associations between the HEI and nutrient intakes. This study updates and expands upon previous findings on these associations. Using German consumption data, where ∼12 million purchases from 13 131 households are recorded, HEI-2010 total and individual scores, as well as several energy and nutrient densities were calculated. Correlations between the HEI and individual energy and nutrient densities were carried out to identify which nutrients are more or less well represented by the HEI. The HEI had the highest correlations with energy density and the densities of water-soluble vitamins (e.g. folic acid) and minerals (e.g. calcium). Weaker associations were identified for the densities of fat-soluble vitamins (e.g. vitamin D) as well as of the vitamins B1 and B12. Negligible correlations were detected for the densities of trace elements (e.g. fluoride and iodine), salt and fat composition. Given that energy intake and the intake of plant-based foods are relevant dietary issues, the HEI-2010 can be defined as a meaningful index to describe diet quality. However, because the intakes of salt, trace elements (e.g. fluoride and iodine) and fat-soluble vitamins, as well as the fat composition may be less reflected, they should be analyzed separately when using the HEI for measuring diet quality.

Dietary patterns of adolescents in Germany--associations with nutrient intake and other health related lifestyle characteristics.

BACKGROUND: The aim of this study was to identify dietary patterns among a representative sample of German adolescents and their associations with energy and nutrient intake, socioeconomic and lifestyle characteristics, and overweight status. METHODS: In the analysis, data from the German Health Interview and Examination Survey for Children and Adolescents were used. The survey included a comprehensive dietary history interview conducted among 1272 adolescents aged 12 to 17 years. Dietary patterns were determined with principal component analysis (PCA) based on 48 food groups, for boys and girls separately. RESULTS: Three dietary patterns among boys and two among girls were identified. Among boys, high adherence to the 'western' pattern was associated with higher age, lower socioeconomic status (SES), and lower physical activity level (PA). High adherence to the 'healthy' pattern among boys, but not among girls, was associated with higher SES, and higher PA. Among boys, high adherence to the 'traditional' pattern was associated with higher age. Among girls, high adherence to the 'traditional and western' pattern was associated with lower age, lower SES and more hours watching TV per day. The nutrient density of several vitamins and minerals, particularly of B-vitamins and calcium, increased with increasing scores of the 'healthy' pattern among both sexes. Conversely, with increasing scores of the 'western' pattern among boys, most nutrient densities decreased, particularly of fibre, beta-carotene, vitamin D, biotin and calcium. Among girls with higher scores of the 'traditional and western' pattern, nutrient densities of vitamin A, C, E, K and folate decreased. Among boys, high adherence to the 'traditional' pattern was correlated with higher densities of vitamin B12 and vitamin D and lower densities of fibre, magnesium and iron. No significant associations between dietary patterns and overweight were found. CONCLUSIONS: Higher scores for dietary patterns characterized by higher consumption of take away food, meat, confectionary and soft drinks ('western' and 'traditional and western') were found particularly among 16- to 17-years old boys and among adolescents with lower SES. These patterns were also associated with higher energy density, higher percent of energy from unsaturated fatty acids and lower percent of energy from carbohydrates as well as lower nutrient densities of several vitamins and minerals. Therefore, nutritional interventions should try to focus more on adolescents with lower SES and boys in general.

Phase 1 Dose Escalation Study of the Allosteric AKT Inhibitor BAY 1125976 in Advanced Solid Cancer-Lack of Association between Activating AKT Mutation and AKT Inhibition-Derived Efficacy.

This open-label, phase I first-in-human study (NCT01915576) of BAY 1125976, a highly specific and potent allosteric inhibitor of AKT1/2, aimed to evaluate the safety, pharmacokinetics, and maximum tolerated dose of BAY 1125976 in patients with advanced solid tumors. Oral dose escalation was investigated with a continuous once daily (QD) treatment (21 days/cycle) and a twice daily (BID) schedule. A dose expansion in 28 patients with hormone receptor-positive metastatic breast cancer, including nine patients harboring the AKT1E17K mutation, was performed at the recommended phase 2 dose (R2D) of 60 mg BID. Dose-limiting toxicities (Grades 3-4) were increased in transaminases, γ-glutamyltransferase (γ-GT), and alkaline phosphatase in four patients in both schedules and stomach pain in one patient. Of the 78 patients enrolled, one patient had a partial response, 30 had stable disease, and 38 had progressive disease. The clinical benefit rate was 27.9% among 43 patients treated at the R2D. AKT1E17K mutation status was not associated with tumor response. Genetic analyses revealed additional mutations that could promote tumor cell growth despite the inhibition of AKT1/2. BAY 1125976 was well tolerated and inhibited AKT1/2 signaling but did not lead to radiologic or clinical tumor responses. Thus, the refinement of a selection of biomarkers for AKT inhibitors is needed to improve their monotherapy activity.

Temporal changes in predicted risk of type 2 diabetes in Germany: findings from the German Health Interview and Examination Surveys 1997-1999 and 2008-2011.

OBJECTIVE: Over time, prevalence changes in individual diabetes risk factors have been observed for Germany and other European countries. We aimed to investigate the temporal change of a summary measure of type 2 diabetes risk in Germany. DESIGN: Comparison of data from two cross-sectional surveys that are about 12 years apart. SETTING: Two nationwide health examination surveys representative for the non-institutionalised population aged 18-79 years in Germany. PARTICIPANTS: The study included participants without diagnosed diabetes from the national health examination surveys in 1997-1999 (n=6457) and 2008-2011 (n=6095). OUTCOME MEASURES: Predicted 5-year type 2 diabetes risk was calculated using the German Diabetes Risk Score (GDRS), which considers information on age, anthropometry, lifestyle factors, hypertension and family history of diabetes. RESULTS: Between the two survey periods, the overall age- and sex-standardised predicted 5-year risk of type 2 diabetes decreased by 27% from 1.5% (95% CI 1.4% to 1.6%) to 1.1% (1.0% to 1.2%). The decrease in red meat intake and waist circumference had the highest impact on the overall decrease in diabetes risk. In stratified analyses, diabetes risk decreased among both sexes and within strata of age and body mass index. Diabetes risk also decreased among highly educated persons, but remained unchanged among persons with a middle or low educational level. CONCLUSIONS: Monitoring type 2 diabetes risk by a summary measure such as the GDRS could essentially contribute to interpret the dynamics in diabetes epidemiology.

Validation of the German Diabetes Risk Score among the general adult population: findings from the German Health Interview and Examination Surveys.

OBJECTIVE: To evaluate the German Diabetes Risk Score (GDRS) among the general adult German population for prediction of incident type 2 diabetes and detection of prevalent undiagnosed diabetes. METHODS: The longitudinal sample for prediction of incident diagnosed type 2 diabetes included 3625 persons who participated both in the examination survey in 1997-1999 and the examination survey in 2008-2011. Incident diagnosed type 2 diabetes was defined as first-time physician diagnosis or antidiabetic medication during 5 years of follow-up excluding potential incident type 1 and gestational diabetes. The cross-sectional sample for detection of prevalent undiagnosed diabetes included 6048 participants without diagnosed diabetes of the examination survey in 2008-2011. Prevalent undiagnosed diabetes was defined as glycated haemoglobin ≥6.5% (48 mmol/mol). We assessed discrimination as area under the receiver operating characteristic curve (ROC-AUC (95% CI)) and calibration through calibration plots. RESULTS: In longitudinal analyses, 82 subjects with incident diagnosed type 2 diabetes were identified after 5 years of follow-up. For prediction of incident diagnosed diabetes, the GDRS yielded an ROC-AUC of 0.87 (0.83 to 0.90). Calibration plots indicated excellent prediction for low diabetes risk and overestimation for intermediate and high diabetes risk. When considering the entire follow-up period of 11.9 years (ROC-AUC: 0.84 (0.82 to 0.86)) and including incident undiagnosed diabetes (ROC-AUC: 0.81 (0.78 to 0.84)), discrimination decreased somewhat. A previously simplified paper version of the GDRS yielded a similar predictive ability (ROC-AUC: 0.86 (0.82 to 0.89)). In cross-sectional analyses, 128 subjects with undiagnosed diabetes were identified. For detection of prevalent undiagnosed diabetes, the ROC-AUC was 0.84 (0.81 to 0.86). Again, the simplified version yielded a similar result (ROC-AUC: 0.83 (0.80 to 0.86)). CONCLUSIONS: The GDRS might be applied for public health monitoring of diabetes risk in the German adult population. Future research needs to evaluate whether the GDRS is useful to improve diabetes risk awareness and prevention among the general population.

Association between hemoglobin A1c and all-cause mortality: results of the mortality follow-up of the German National Health Interview and Examination Survey 1998.

OBJECTIVE: This study examined the association of HbA1c-defined glycemic status and continuous HbA1c with all-cause mortality. RESEARCH DESIGN AND METHODS: The study population comprised 6,299 participants (aged 18-79 years) of the German National Health Interview and Examination Survey 1998, who were followed up for mortality for an average of 11.6 years. Glycemic status was defined as known diabetes (self-reported diagnosis or intake of antidiabetic medication) and based on HbA1c levels according to American Diabetes Association diagnostic criteria as undiagnosed diabetes (≥6.5% [≥48 mmol/mol]), prediabetes with very high (6.0-6.4% [42-46 mmol/mol]) or high diabetes risk (5.7-5.9% [39-41 mmol/mol]), and normoglycemia (<5.7% [<39 mmol/mol]). Associations between glycemic status and mortality were examined by Cox regression adjusting for age, sex, education, lifestyle factors, anthropometric measures, and history of chronic diseases (reference: normoglycemia). Spline models were fitted to investigate associations between continuous HbA1c and mortality among participants without known diabetes. RESULTS: Excess mortality risk was observed for participants with known diabetes (hazard ratio 1.41 [95% CI 1.08-1.84]) and undiagnosed diabetes (1.63 [1.23-2.17]) but not for those with high (1.02 [0.80-1.30]) or very high diabetes risk (0.87 [0.67-1.13]). Spline models revealed a U-shaped association, with lowest risk at HbA1c levels 5.4-5.6% (36-38 mmol/mol) and a significantly increased risk at ≤5.0% (≤31 mmol/mol) and ≥6.4% (≥46 mmol/mol). CONCLUSIONS: Unlike known and undiagnosed diabetes, HbA1c levels in the prediabetic range were not associated with an increased mortality risk. The observed U-shaped relationship adds to existing evidence that not only high but also low HbA1c levels might be associated with all-cause mortality.

Associations of dietary indices with biomarkers of dietary exposure and cardiovascular status among adolescents in Germany.

BACKGROUND: Adolescence is an important life stage for the development of dietary preferences and health behaviour. Longitudinal studies indicated that cardiovascular status in adolescence predicts cardiovascular risk marker values in adulthood. Several diet quality indices for adolescents have been developed in the past, but literature concerning associations between indices and biomarkers of dietary exposure and cardiovascular status is rather sparse. Hence, the aim of this study was to analyse associations of dietary indices with biomarkers of dietary exposure and cardiovascular status. METHODS: For the present analysis, data from the German Health Interview and Examination Survey for Children and Adolescents (KiGGS 2003-2006) were used. The analysis included 5,198 adolescents, aged 12 to 17 years. The Healthy Food Diversity Index (HFD), the Healthy Nutrition Score for Kids and Youth (HuSKY), the Indicator Food Index (IFI) and a simple fruit/vegetable intake index were derived from food frequency questionnaire information to indicate a healthy diet. Adjusted mean values for homocysteine, uric acid, CRP, total cholesterol, HDL-C, ferritin, HbA1c, folate, vitamin B12 and BMI were calculated using complex-samples general linear models for quintiles of the different indices. Furthermore, the agreement in ranking between the different indices was calculated by weighted kappa. All statistical analyses were conducted for boys and girls separately, and were adjusted for potential confounders. RESULTS: Folate was positively associated with the HFD, the HuSKY, and fruit/vegetable intake for both boys and girls and with IFI for boys. Among girls, positive associations were seen between vitamin B12 and the IFI and between diastolic blood pressure and the IFI as well as fruit/vegetable intake. A negative association was found between homocysteine and the HFD, the HuSKY, and the IFI for both boys and girls and with fruit/vegetable intake for boys. Among boys, uric acid and HbA1c were negatively and prevalence of obesity positively associated with the IFI. CONCLUSIONS: Overall, the indices, even the simpler ones, seem to have a similar general capability in predicting biomarkers of dietary exposure. To predict risk of cardiovascular disease dietary indices may have to be more specific.

A new index to measure healthy food diversity better reflects a healthy diet than traditional measures.

The recommendation to eat diverse types of foodstuffs is an internationally accepted recommendation for a healthy diet. The importance of dietary variety is based on several studies that have shown that diverse diets are accompanied by positive health outcomes. However, the definition and measurement of healthy food diversity are often criticized in the literature. Nutritional studies generally use count indices to quantify food diversity. As these measures have considerable disadvantages, several nutritionists have called for a precise definition and measurement of food diversity. This study aimed to develop a new healthy food diversity indicator. This index is based on a distribution measure mainly applied in economic and ecological studies. It considers 3 aspects important for healthy food diversity: number, distribution, and health value of consumed foods. We have validated the new index using energy-adjusted correlations with diet quality indicators. A comparison with selected traditional diversity indices revealed that the new indicator more appropriately reflected healthy food diversity.

Determinants of diet quality.

BACKGROUND: An unbalanced diet is a main risk factor for several chronic diseases. This paper identifies groups of individuals with an unbalanced diet based on the consumption of nutrients. A characterisation of the groups may help to focus efforts aimed at improving the dietary behaviour of the population. METHODS: Using nutritional data of 1763 men and 2267 women participating in the German Nutrition Survey of 1998, we constructed two indices for diet quality that each combines a large amount of nutrients into a single indicator. The impact of sociodemographic and lifestyle characteristics on the diet quality indices was analysed using multiple regression analyses. RESULTS: The results show a considerable variation of diet quality between different groups of individuals. High diet quality in terms of the consumption of vitamins, minerals and trace elements is positively associated with income, education level, age, energy intake, food diversity, sport activity and vegetarianism. On the other hand, a low diet quality as indicated by high intakes of e.g. fat, sugar, alcohol and sodium can be expected when energy intake is high, for individuals of middle age and for pregnant and breast-feeding women. CONCLUSION: The results of this study help to identify groups of individuals with preferable and non-preferable diet quality. For developing public health strategies, in particular the impact of age on diet quality seems to be interesting. The rising diet quality with increasing age could reflect a changing health consciousness. It could thus be a challenge for health policy to promote a healthy way of living focused especially on young individuals.